Abstract 5465
Background
Dense stroma is a hallmark of hard-to-treat cancers such as pancreatic adenocarcinoma. VCN-01 oncolytic adenovirus is designed to replicate in cancer cells with dysfunctional RB1 pathway, improve tumor targeting and express hyaluronidase to enhance virus intratumor spreading and facilitate drug extravasation into the tumor.
Methods
The mechanisms of action of VCN-01 were tested in pancreatic xenograft models after both intravenous and intratumor administration. In a proof of concept phase I clinical trial study (8 patients), VCN-01 was escalated up to 1E+11vp per Endoscopic Ultrasound (EUS)-guided intratumor injection (3x) combined with the standard of care, SoC (gemcitabine or nab-paclitaxel/gemcitabine) in patients with advanced pancreatic adenocarcinoma.
Results
VCN-01 alone showed antitumor efficacy in preclinical models and further increased its efficacy when combined with SoC chemotherapy. VCN-01 replicated within injected tumors regardless of chemotherapy. Hyaluronidase expression by VCN-01 facilitated tumor extravasation and increased uptake of chemotherapy agents and antibodies. Data obtained from a phase 1 clinical trial of VCN-01 administered by repeated intratumor injection showed that the combination treatment was generally well-tolerated although dose limiting toxicity was found at highest dose. When combined with chemotherapy, VCN-01 stabilized the injected lesion in all patients, with a patient showing long progression free survival of 134 weeks. VCN-01 was detected as secondary peaks in blood several days after injection and in tumors at day 20-28, indicating virus replication. Hyaluronidase PH20 presence in sera was confirmed for all patients injected at 1E+11vp. Elastography of VCN-01-treated tumors evidenced reduction in tumor stiffness regardless of nab-paclitaxel co-administration.
Conclusions
VCN-01 replicates and expresses hyaluronidase after intratumor injection both in preclinical models and in patients with pancreatic cancer. Enhanced chemotherapy access and reduction of tumor stiffness favours local control of pancreatic tumours treated with VCN-01 + standard of care.
Clinical trial identification
EudraCT: 2012-005556-42.
Editorial acknowledgement
Legal entity responsible for the study
VCN Biosciences.
Funding
VCN Biosciences.
Disclosure
M. Hidalgo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): EMD; Speaker Bureau / Expert testimony: Ipsem; Speaker Bureau / Expert testimony: Shire; Advisory / Consultancy: SOBI; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Champions Oncology; Advisory / Consultancy: Agenus; Advisory / Consultancy: Erytech; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Pharmacyte; Advisory / Consultancy: Bioline; Advisory / Consultancy, Shareholder / Stockholder / Stock options: BioOncotech; Advisory / Consultancy, Research grant / Funding (institution): Oncomatrix; Advisory / Consultancy: VCN Biosciences; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Nelum; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Eng T Cells. M. Bazan-Peregrino: Full / Part-time employment: VCN Biosciences. B. Laquente: Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Servier; Research grant / Funding (institution): Mylan. R. Alvarez Gallego: Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Shire. A. Mato-Berciano: Full / Part-time employment: VCN Biosciences. M. Giménez-Alejandre: Full / Part-time employment: VCN Biosciences. V. Maliandi: Full / Part-time employment: VCN Biosciences. M.C. Riesco Martinez: Speaker Bureau / Expert testimony: Merck. M. Perez-Carreras: Advisory / Consultancy: Intercept; Research grant / Funding (institution): GENFIT. G. Capella: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: VCN Biosciences. R. Alemany: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: VCN Biosciences; Research grant / Funding (institution): Lokon Pharma; Research grant / Funding (institution): Mologen. R. Salazar: Advisory / Consultancy, Research grant / Funding (institution): VCN Biosciences; Advisory / Consultancy: Agendia; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Roche Diagnostics; Advisory / Consultancy: Ferrer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche Farma; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AZD; Speaker Bureau / Expert testimony: Celgene; Leadership role, Shareholder / Stockholder / Stock options: Sace MedHealth; Research grant / Funding (institution): PsiOxus; Research grant / Funding (institution): Mologen. E. Blasi: Full / Part-time employment: VCN Biosciences. C. Blasco: Full / Part-time employment: VCN Biosciences. M. Cascallo: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: VCN Biosciences. R. Garcia-Carbonero: Advisory / Consultancy: AAA; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Servier; Research grant / Funding (institution): ARMO; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): VCN Biosciences. All other authors have declared no conflicts of interest.
Resources from the same session
5189 - Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Presenter: Laura Moliner
Session: Poster Display session 1
Resources:
Abstract
3539 - Prognostic role of RLF/MYCL1 and circPVT1 in SCLC.
Presenter: Clelia Tiziana Storlazzi
Session: Poster Display session 1
Resources:
Abstract
3438 - High-biologically effective dose radiotherapy improve the survival of small cell lung cancer patients with brain metastases: a propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster Display session 1
Resources:
Abstract
3232 - Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3633 - Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Presenter: Carminia Maria Della Corte
Session: Poster Display session 1
Resources:
Abstract
3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer
Presenter: Yamei Chen
Session: Poster Display session 1
Resources:
Abstract
5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer
Presenter: Alejandro Navarro Mendivil
Session: Poster Display session 1
Resources:
Abstract
5997 - Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer (SCLC): The PAVE study, a Hellenic Cooperative Oncology Group Study
Presenter: Helena Linardou
Session: Poster Display session 1
Resources:
Abstract
4502 - Tobacco use in lung cáncer (LC) patients (p) in Spain
Presenter: Enric Carcereny Costa
Session: Poster Display session 1
Resources:
Abstract
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract